Pharmacological Treatment of Angina PDF

Treatment of Angina Dr Alun Hughes Coronary blood flow through left ventricle Rang and Dale’s Pharmacology (figure 21.5 page 251 in 7th Ed, page 252 in 8th Ed) What shrinks the window? • Shortening diastole – e.g. increased heart rate • Increased ventricular end diastolic pressure – e.g. aorti...

Treatment of Angina Dr Alun Hughes Coronary blood flow through left ventricle Rang and Dale’s Pharmacology (figure 21.5 page 251 in 7th Ed, page 252 in 8th Ed) What shrinks the window? • Shortening diastole – e.g. increased heart rate • Increased ventricular end diastolic pressure – e.g. aortic valve stenosis • Reduced diastolic arterial pressure – e.g. mitral or aortic valve incompetence, heart failure 3 Coronary ischaemia and infarction • Coronary ischaemia usually the result of atherosclerosis – Causes angina • Sudden ischaemia is usually caused by thrombosis – May result in cardiac infarction • Coronary spasms sometimes causes angina – “variant” angina • Cellular calcium overload results from ischaemia – may cause cell death and dysrhythmias 4 Angina Pectoris • Chest pain due to inadequate supply of oxygen to the heart – Typically severe and crushing – “Tight, constricting, dull or heavy” – SIGN Guidelines • Characteristic distribution of pain – Often retrosternal, or left side of chest and can radiate to left arm, neck, jaw and back – Brought on by exertion, cold or excitement – Thought chemical factors that cause pain in skeletal muscle (i.e K+, H+ and adenosine) are responsible • Angina can accompany or be a precursor of a heart attack Angina classes 6 Angina classes • Stable Angina – Predictable chest pain on exertion – Caused by a fixed narrowing of the coronary arteries • Unstable Angina – Occurs at rest and with less exertion than stable angina – Associated with a thrombus around a ruptured atheromatous plaque but without complete occlusion of the vessel (similar to MI) • Variant (Prinzmetal) Angina – Uncommon – Caused by coronary artery spasm – Not completely understood, but sometimes associated with atherosclerosis 7 Lilly, Pathophys of Heart Disease 6e: Figure 6.5 8 Overview of treatment Treatments to reduce chest pain symptoms: – – – – – – Beta-blockers Nitrates Calcium channel antagonists Nirocandil Ivabradine Ranolazine Treatments to prolong survival: – – – – – Beta-blockers Aspirin Statins (Angiotensin Converting Enzyme Inhibitors) (Angiotensin II Receptor Blockers) Treatment of symptoms • Offer short-acting nitrate for preventing/treating episodes of angina. • Offer first-line treatment: – Usually a β-blocker, but a calcium channel blocker (CCB) can be considered. • If control by β-blockers not optimal, addition of CCB can be considered. • If beta blocker or CCB monotherapy ineffective and the other option is contraindicated, there are a few other drugs may be additionally used (e.g. nicorandil or ivabradine). Antianginal drugs • Mainly work by ↓ the metabolic demand of the muscle • Organic nitrates, nicorandil and calcium antagonists are vasodilators – ↓ preload or aHerload • b-blockers and ivabradine slow down the heart – ↓ the metabolic demand of the muscle 11 Organic Nitrates • Glyceryl trinitrate and isosorbide mononitrate – Powerful vasodilators – Work by being metabolised to nitric oxide (NO) and relax smooth muscle (particular vascular smooth muscle) – Act on veins to ↓ cardiac preload • Higher concentrations can affect arteries,  ↓ aHerload – ↓ cardiac workload is helped by dilaIon of collateral coronary vessels •  Improves distribution of coronary blood flow towards ischaemic areas • Dilation of constricted coronary vessels is particularly beneficial in variant angina 12 Role of the endothelial cells in regulating vascular tone Guyton p196 12th ed, p208 13th ed Rang and Dale’s Pharmacology (figure 21.11 page 260 in 7th Ed page 261 in 8th Ed) Clinical Uses of Organic Nitrates in Angina • Stable Angina – Prevention by sublingual glyceryl trinitrate shortly before exertion or isosorbide mononitrate long before • Unstable angina – intravenous glyceryl trinitrate (GTN) • Unwanted effects are common, headache and postural hypotension may occur 15 Other Clinical Uses of Organic Nitrates • Acute heart failure (in specific circumstances) – intravenous GTN • Chronic Heart Failure (CHF) – isosorbide mononitrate with hydralazine in patients of African American origin especially, (or patient cannot tolerate more commonly used CHF drugs) 16 b-blockers • Important (first line treatment) in the prophylaxis and treatment of stable and unstable angina • ↓ cardiac oxygen consumpIon by slowing the heart • Also have an antidysrhythmic action – reduce death after MI • Bisoprolol, Atenolol 17 Calcium Channel Blockers (CCBs) • Preventing opening of voltage-gated L-type Ca2+ channels –  block Ca2+ entry – Mainly affect the heart and smooth muscle to inhibit calcium entry upon muscle cell depolarisation • Two main types: – Dihydropyridine derivatives, e.g. amlodipine and lercanidipine – Rate-limiting, e.g. verapamil and diltiazem • Vasodilator effect mainly on resistance vessels –  reduces afterload – also dilate coronary vessels (important in variant angina) • Verapamil and diltiazem can reduce and impair AV conduction and myocardial contractility Clinical Uses of CCBs in Angina • Choice depends on comorbidity and drug interactions – Amlodipine or lercanidipine safe in patients with heart failure, used instead of a Beta-Blocker in Prinzmetal angina or alongside beta-blockers in most angina – Diltiazem or verapamil used but contraindicated in heart failure, bradycardia, AV block or in presence of Beta-Blocker • Side effects include: – headache, constipation, ankle oedema 19 Other Clinical Uses of CCBs • Antidysrhythmics – Mainly verapamil • Slows ventricular rate in rapid atrial fibrillation • Prevents recurrence of supraventricular tachycardia (SVT) • No effect on ventricular arrhythmias • Hypertension – Mainly amlodipine or lercanidpine 20 Potassium Channel Activators • Nicorandil – combines activation of potassium K+ATP channels with nitrovasodilator actions • Causes hyperpolarisation of vascular smooth muscle – both an arterial and venous dilator – causes headaches, flushing and dizziness – used for patients who remain symptomatic despite optimal management with other drugs 21 Other anti-anginals • Ivabradine – Inhibits funny “f”-type channels in heart – Reduces cardiac pacemaker activity •  inhibits heart rate • Ranolazine – Unique anti-anginal used as a last resort 22 Learning Outcomes Explain the pathology underlying the different categories of angina. Categorise the drugs used to treat the symptoms of angina and those that prolong survival. Relate the mechanism of action of drugs to used to treat the symptoms of angina to their therapeutic outcome and side-effects.